Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH
This study aimed to examine the in vivo and in vitro therapeutic effects of glycyrrhizic acid (GA) on steroid-induced osteonecrosis of the femoral head (SONFH), which is caused by the overuse of glucocorticoids (GCs). Clinically, we identified elevated oxidative stress (OS) levels and an imbalance i...
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| creator | Xu, Huihui Fang, Liang Zeng, Qinghe Chen, Jiali Ling, Houfu Xia, Hanting Ge, Qinwen Wu, Congzi Zou, Kaiao Wang, Xu Wang, Pinger Yuan, Wenhua Dong, Rui Hu, Songfeng Xiao, Luwei He, Bangjian Tong, Peijian Jin, Hongting |
| description | This study aimed to examine the
in vivo
and
in vitro
therapeutic effects of glycyrrhizic acid (GA) on steroid-induced osteonecrosis of the femoral head (SONFH), which is caused by the overuse of glucocorticoids (GCs). Clinically, we identified elevated oxidative stress (OS) levels and an imbalance in osteolipogenic homeostasis in SONFH patients compared to femoral neck fracture (FNF) patients.
In vivo
, we established experimental SONFH in rats
via
lipopolysaccharides (LPSs) combined with methylprednisolone (MPS). We showed that GA and Wnt agonist-S8320 alleviated SONFH, as evidenced by the reduced microstructural and histopathological alterations in the subchondral bone of the femoral head and the decreased levels of OS in rat models.
In vitro
, GA reduced dexamethasone (Dex)-induced excessive NOX4 and OS levels by activating the Wnt/β-catenin pathway, thereby promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibiting lipogenic differentiation. In addition, GA regulated the expression levels of the key transcription factors downstream of this pathway, Runx2 and PPARγ, thus maintaining osteolipogenic homeostasis. In summary, we demonstrated for the first time that GA modulates the osteolipogenic differentiation commitment of MSCs induced by excessive OS through activating the Wnt/β-catenin pathway, thereby ameliorating SONFH.
GA can reduce the level of OS induced by excessive GCs through the activation of the Wnt/β-catenin signaling pathway, thereby maintaining the osteolipogenic homeostasis of MSCs. |
| doi_str_mv | 10.1039/d2fo02337g |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2768179868</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2756670977</sourcerecordid><originalsourceid>FETCH-LOGICAL-c373t-c01ebd38627f0e1947b8bb7d35fcc38ea2c1107eef88e3c1da0ae4031ede5f403</originalsourceid><addsrcrecordid>eNpdkc9u1DAQxiMEolXphTvIEheEFOo_Sewc0cJukQp7KAhukWOPu64SO9hOIbwI78GD8Ey43bZIzGVG8_3m00hfUTwl-DXBrD3R1HhMGeMXD4pDiitaNjX--vBurtrmoDiO8RLnYm0rWvG4OGBNXREq6sPi12ZY1BLCzv60CkllNZJDghBR2gHaLRME_8NqmewVoJgCxFhap2cFGmlrDARwyWbZO6T8ONo05gXyBn04X0XUL9kz32bAXdxYfnHp5M_vUskEzjo0ybT7LheUPJoCXF3fnm8_rk-fFI-MHCIc3_aj4vP63afVaXm23bxfvTkrFeMslQoT6DUTDeUGA2kr3ou-55rVRikmQFJFCOYARghgimiJJVSYEdBQmzwcFS_3vlPw32aIqRttVDAM0oGfY0d53TQct5xn9MV_6KWfg8vfZaoRhLeiEZl6tadU8DEGMN0U7CjD0hHcXSfWvaXr7U1imww_v7Wc-xH0PXqXTwae7YEQ1b36L3L2Fxjpnog</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2768179868</pqid></control><display><type>article</type><title>Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH</title><source>MEDLINE</source><source>Royal Society Of Chemistry Journals 2008-</source><creator>Xu, Huihui ; Fang, Liang ; Zeng, Qinghe ; Chen, Jiali ; Ling, Houfu ; Xia, Hanting ; Ge, Qinwen ; Wu, Congzi ; Zou, Kaiao ; Wang, Xu ; Wang, Pinger ; Yuan, Wenhua ; Dong, Rui ; Hu, Songfeng ; Xiao, Luwei ; He, Bangjian ; Tong, Peijian ; Jin, Hongting</creator><creatorcontrib>Xu, Huihui ; Fang, Liang ; Zeng, Qinghe ; Chen, Jiali ; Ling, Houfu ; Xia, Hanting ; Ge, Qinwen ; Wu, Congzi ; Zou, Kaiao ; Wang, Xu ; Wang, Pinger ; Yuan, Wenhua ; Dong, Rui ; Hu, Songfeng ; Xiao, Luwei ; He, Bangjian ; Tong, Peijian ; Jin, Hongting</creatorcontrib><description>This study aimed to examine the
in vivo
and
in vitro
therapeutic effects of glycyrrhizic acid (GA) on steroid-induced osteonecrosis of the femoral head (SONFH), which is caused by the overuse of glucocorticoids (GCs). Clinically, we identified elevated oxidative stress (OS) levels and an imbalance in osteolipogenic homeostasis in SONFH patients compared to femoral neck fracture (FNF) patients.
In vivo
, we established experimental SONFH in rats
via
lipopolysaccharides (LPSs) combined with methylprednisolone (MPS). We showed that GA and Wnt agonist-S8320 alleviated SONFH, as evidenced by the reduced microstructural and histopathological alterations in the subchondral bone of the femoral head and the decreased levels of OS in rat models.
In vitro
, GA reduced dexamethasone (Dex)-induced excessive NOX4 and OS levels by activating the Wnt/β-catenin pathway, thereby promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibiting lipogenic differentiation. In addition, GA regulated the expression levels of the key transcription factors downstream of this pathway, Runx2 and PPARγ, thus maintaining osteolipogenic homeostasis. In summary, we demonstrated for the first time that GA modulates the osteolipogenic differentiation commitment of MSCs induced by excessive OS through activating the Wnt/β-catenin pathway, thereby ameliorating SONFH.
GA can reduce the level of OS induced by excessive GCs through the activation of the Wnt/β-catenin signaling pathway, thereby maintaining the osteolipogenic homeostasis of MSCs.</description><identifier>ISSN: 2042-6496</identifier><identifier>EISSN: 2042-650X</identifier><identifier>DOI: 10.1039/d2fo02337g</identifier><identifier>PMID: 36541285</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Animal models ; Animals ; beta Catenin - metabolism ; Cbfa-1 protein ; Cell Differentiation ; Dexamethasone ; Differentiation (biology) ; Femur ; Glucocorticoids ; Glycyrrhizic Acid - pharmacology ; Homeostasis ; In vivo methods and tests ; Lipopolysaccharides ; Mesenchymal Stem Cells - metabolism ; Mesenchyme ; Methylprednisolone ; NOX4 protein ; Osteogenesis ; Osteonecrosis ; Oxidative stress ; Rats ; Stem cell transplantation ; Stem cells ; Subchondral bone ; Transcription factors ; Wnt protein ; Wnt Signaling Pathway ; β-Catenin</subject><ispartof>Food & function, 2023-01, Vol.14 (2), p.946-96</ispartof><rights>Copyright Royal Society of Chemistry 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c373t-c01ebd38627f0e1947b8bb7d35fcc38ea2c1107eef88e3c1da0ae4031ede5f403</citedby><cites>FETCH-LOGICAL-c373t-c01ebd38627f0e1947b8bb7d35fcc38ea2c1107eef88e3c1da0ae4031ede5f403</cites><orcidid>0000-0001-7770-7600</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36541285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Huihui</creatorcontrib><creatorcontrib>Fang, Liang</creatorcontrib><creatorcontrib>Zeng, Qinghe</creatorcontrib><creatorcontrib>Chen, Jiali</creatorcontrib><creatorcontrib>Ling, Houfu</creatorcontrib><creatorcontrib>Xia, Hanting</creatorcontrib><creatorcontrib>Ge, Qinwen</creatorcontrib><creatorcontrib>Wu, Congzi</creatorcontrib><creatorcontrib>Zou, Kaiao</creatorcontrib><creatorcontrib>Wang, Xu</creatorcontrib><creatorcontrib>Wang, Pinger</creatorcontrib><creatorcontrib>Yuan, Wenhua</creatorcontrib><creatorcontrib>Dong, Rui</creatorcontrib><creatorcontrib>Hu, Songfeng</creatorcontrib><creatorcontrib>Xiao, Luwei</creatorcontrib><creatorcontrib>He, Bangjian</creatorcontrib><creatorcontrib>Tong, Peijian</creatorcontrib><creatorcontrib>Jin, Hongting</creatorcontrib><title>Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH</title><title>Food & function</title><addtitle>Food Funct</addtitle><description>This study aimed to examine the
in vivo
and
in vitro
therapeutic effects of glycyrrhizic acid (GA) on steroid-induced osteonecrosis of the femoral head (SONFH), which is caused by the overuse of glucocorticoids (GCs). Clinically, we identified elevated oxidative stress (OS) levels and an imbalance in osteolipogenic homeostasis in SONFH patients compared to femoral neck fracture (FNF) patients.
In vivo
, we established experimental SONFH in rats
via
lipopolysaccharides (LPSs) combined with methylprednisolone (MPS). We showed that GA and Wnt agonist-S8320 alleviated SONFH, as evidenced by the reduced microstructural and histopathological alterations in the subchondral bone of the femoral head and the decreased levels of OS in rat models.
In vitro
, GA reduced dexamethasone (Dex)-induced excessive NOX4 and OS levels by activating the Wnt/β-catenin pathway, thereby promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibiting lipogenic differentiation. In addition, GA regulated the expression levels of the key transcription factors downstream of this pathway, Runx2 and PPARγ, thus maintaining osteolipogenic homeostasis. In summary, we demonstrated for the first time that GA modulates the osteolipogenic differentiation commitment of MSCs induced by excessive OS through activating the Wnt/β-catenin pathway, thereby ameliorating SONFH.
GA can reduce the level of OS induced by excessive GCs through the activation of the Wnt/β-catenin signaling pathway, thereby maintaining the osteolipogenic homeostasis of MSCs.</description><subject>Animal models</subject><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Cbfa-1 protein</subject><subject>Cell Differentiation</subject><subject>Dexamethasone</subject><subject>Differentiation (biology)</subject><subject>Femur</subject><subject>Glucocorticoids</subject><subject>Glycyrrhizic Acid - pharmacology</subject><subject>Homeostasis</subject><subject>In vivo methods and tests</subject><subject>Lipopolysaccharides</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mesenchyme</subject><subject>Methylprednisolone</subject><subject>NOX4 protein</subject><subject>Osteogenesis</subject><subject>Osteonecrosis</subject><subject>Oxidative stress</subject><subject>Rats</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Subchondral bone</subject><subject>Transcription factors</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway</subject><subject>β-Catenin</subject><issn>2042-6496</issn><issn>2042-650X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9u1DAQxiMEolXphTvIEheEFOo_Sewc0cJukQp7KAhukWOPu64SO9hOIbwI78GD8Ey43bZIzGVG8_3m00hfUTwl-DXBrD3R1HhMGeMXD4pDiitaNjX--vBurtrmoDiO8RLnYm0rWvG4OGBNXREq6sPi12ZY1BLCzv60CkllNZJDghBR2gHaLRME_8NqmewVoJgCxFhap2cFGmlrDARwyWbZO6T8ONo05gXyBn04X0XUL9kz32bAXdxYfnHp5M_vUskEzjo0ybT7LheUPJoCXF3fnm8_rk-fFI-MHCIc3_aj4vP63afVaXm23bxfvTkrFeMslQoT6DUTDeUGA2kr3ou-55rVRikmQFJFCOYARghgimiJJVSYEdBQmzwcFS_3vlPw32aIqRttVDAM0oGfY0d53TQct5xn9MV_6KWfg8vfZaoRhLeiEZl6tadU8DEGMN0U7CjD0hHcXSfWvaXr7U1imww_v7Wc-xH0PXqXTwae7YEQ1b36L3L2Fxjpnog</recordid><startdate>20230123</startdate><enddate>20230123</enddate><creator>Xu, Huihui</creator><creator>Fang, Liang</creator><creator>Zeng, Qinghe</creator><creator>Chen, Jiali</creator><creator>Ling, Houfu</creator><creator>Xia, Hanting</creator><creator>Ge, Qinwen</creator><creator>Wu, Congzi</creator><creator>Zou, Kaiao</creator><creator>Wang, Xu</creator><creator>Wang, Pinger</creator><creator>Yuan, Wenhua</creator><creator>Dong, Rui</creator><creator>Hu, Songfeng</creator><creator>Xiao, Luwei</creator><creator>He, Bangjian</creator><creator>Tong, Peijian</creator><creator>Jin, Hongting</creator><general>Royal Society of Chemistry</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7770-7600</orcidid></search><sort><creationdate>20230123</creationdate><title>Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH</title><author>Xu, Huihui ; Fang, Liang ; Zeng, Qinghe ; Chen, Jiali ; Ling, Houfu ; Xia, Hanting ; Ge, Qinwen ; Wu, Congzi ; Zou, Kaiao ; Wang, Xu ; Wang, Pinger ; Yuan, Wenhua ; Dong, Rui ; Hu, Songfeng ; Xiao, Luwei ; He, Bangjian ; Tong, Peijian ; Jin, Hongting</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-c01ebd38627f0e1947b8bb7d35fcc38ea2c1107eef88e3c1da0ae4031ede5f403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>Cbfa-1 protein</topic><topic>Cell Differentiation</topic><topic>Dexamethasone</topic><topic>Differentiation (biology)</topic><topic>Femur</topic><topic>Glucocorticoids</topic><topic>Glycyrrhizic Acid - pharmacology</topic><topic>Homeostasis</topic><topic>In vivo methods and tests</topic><topic>Lipopolysaccharides</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mesenchyme</topic><topic>Methylprednisolone</topic><topic>NOX4 protein</topic><topic>Osteogenesis</topic><topic>Osteonecrosis</topic><topic>Oxidative stress</topic><topic>Rats</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Subchondral bone</topic><topic>Transcription factors</topic><topic>Wnt protein</topic><topic>Wnt Signaling Pathway</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Huihui</creatorcontrib><creatorcontrib>Fang, Liang</creatorcontrib><creatorcontrib>Zeng, Qinghe</creatorcontrib><creatorcontrib>Chen, Jiali</creatorcontrib><creatorcontrib>Ling, Houfu</creatorcontrib><creatorcontrib>Xia, Hanting</creatorcontrib><creatorcontrib>Ge, Qinwen</creatorcontrib><creatorcontrib>Wu, Congzi</creatorcontrib><creatorcontrib>Zou, Kaiao</creatorcontrib><creatorcontrib>Wang, Xu</creatorcontrib><creatorcontrib>Wang, Pinger</creatorcontrib><creatorcontrib>Yuan, Wenhua</creatorcontrib><creatorcontrib>Dong, Rui</creatorcontrib><creatorcontrib>Hu, Songfeng</creatorcontrib><creatorcontrib>Xiao, Luwei</creatorcontrib><creatorcontrib>He, Bangjian</creatorcontrib><creatorcontrib>Tong, Peijian</creatorcontrib><creatorcontrib>Jin, Hongting</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Food & function</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Huihui</au><au>Fang, Liang</au><au>Zeng, Qinghe</au><au>Chen, Jiali</au><au>Ling, Houfu</au><au>Xia, Hanting</au><au>Ge, Qinwen</au><au>Wu, Congzi</au><au>Zou, Kaiao</au><au>Wang, Xu</au><au>Wang, Pinger</au><au>Yuan, Wenhua</au><au>Dong, Rui</au><au>Hu, Songfeng</au><au>Xiao, Luwei</au><au>He, Bangjian</au><au>Tong, Peijian</au><au>Jin, Hongting</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH</atitle><jtitle>Food & function</jtitle><addtitle>Food Funct</addtitle><date>2023-01-23</date><risdate>2023</risdate><volume>14</volume><issue>2</issue><spage>946</spage><epage>96</epage><pages>946-96</pages><issn>2042-6496</issn><eissn>2042-650X</eissn><abstract>This study aimed to examine the
in vivo
and
in vitro
therapeutic effects of glycyrrhizic acid (GA) on steroid-induced osteonecrosis of the femoral head (SONFH), which is caused by the overuse of glucocorticoids (GCs). Clinically, we identified elevated oxidative stress (OS) levels and an imbalance in osteolipogenic homeostasis in SONFH patients compared to femoral neck fracture (FNF) patients.
In vivo
, we established experimental SONFH in rats
via
lipopolysaccharides (LPSs) combined with methylprednisolone (MPS). We showed that GA and Wnt agonist-S8320 alleviated SONFH, as evidenced by the reduced microstructural and histopathological alterations in the subchondral bone of the femoral head and the decreased levels of OS in rat models.
In vitro
, GA reduced dexamethasone (Dex)-induced excessive NOX4 and OS levels by activating the Wnt/β-catenin pathway, thereby promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibiting lipogenic differentiation. In addition, GA regulated the expression levels of the key transcription factors downstream of this pathway, Runx2 and PPARγ, thus maintaining osteolipogenic homeostasis. In summary, we demonstrated for the first time that GA modulates the osteolipogenic differentiation commitment of MSCs induced by excessive OS through activating the Wnt/β-catenin pathway, thereby ameliorating SONFH.
GA can reduce the level of OS induced by excessive GCs through the activation of the Wnt/β-catenin signaling pathway, thereby maintaining the osteolipogenic homeostasis of MSCs.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>36541285</pmid><doi>10.1039/d2fo02337g</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-7770-7600</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animal models Animals beta Catenin - metabolism Cbfa-1 protein Cell Differentiation Dexamethasone Differentiation (biology) Femur Glucocorticoids Glycyrrhizic Acid - pharmacology Homeostasis In vivo methods and tests Lipopolysaccharides Mesenchymal Stem Cells - metabolism Mesenchyme Methylprednisolone NOX4 protein Osteogenesis Osteonecrosis Oxidative stress Rats Stem cell transplantation Stem cells Subchondral bone Transcription factors Wnt protein Wnt Signaling Pathway β-Catenin |
| title | Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH |
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